This proposal is a request for salary support through a Research Career Development Award for Garold S. Yost. The award would allow Dr. Yost to spend full time in research of mechanisms of pneumotoxicity of xenobiotics. Prior work in Dr. Yost's laboratory included the mechanisms of bioactivation and organ and species selectivity of the pneumotoxin 3- methylindole (3MI). An RCDA would allow Dr. Yost to study selective toxicity to pulmonary tissues of several known pneumotoxins, such as 3MI, 2-methylnaphthalene, and butylated hydroxytoluene, and to extend his studies to other alkyl substituted aromatic compounds. these studies may permit predictions of the structural features of compounds that may be pneumotoxic and lead to an understanding of the precise biochemical, cellular, and physiological bases for the selective damage by these xenobiotics to lung tissue. The research will utilize a number of chemical, biochemical, cellula, isolated organ and whole animal techniques to evaluate the mechanisms whereby a series of pneumotoxins are bioactivated to toxic intermediates and/or detoxified by metabolic process involved in organ-selective pneumotoxicity and will lead to a better understanding of the risks involved in exposure of animals, including humans to these toxicants.